Diabetes mellitus is a complex disease influenced by the genetics of the individual and his environment. The insulin-secreting beta cells of the pancreas remain at the focus of attention in determining the causes of the disease and developing methods for its treatment. Work with experimental animals and their isolated tissues has provided valuable information relevant to the disease in man. The proposed study will examine the role of genetics and environmental factors in the etiology of diabetes using mice and their cells. Specifically we wish to determine: (1) the applicability of flow analysis-cell sorting to completely purify the alpha, beta and delta cells from the islets of Langerhans of the pancreas; (2) the intrinsic susceptibility of cultured islet cells to common human viruses in the absence of other host's immune defense mechanisms; (3) the role of host genetics and virus adaptation to the beta cells in the development of diabetes; and (4) the applicability of using purified, cultured beta cells to reconstitute a diabetic host, by transplantation, as a means of diabetic therapy.